Pathogenesis of bone fragility in women and men

Seeman, Ego

doi:10.1016/s0140-6736(02)08706-8

Cited by 909Bone health and osteoporosis researchBone Metabolism and DiseasesBone fractures and treatments

Pathogenesis of bone fragility in women and men

Seeman, Ego·2002·The Lancet

DOI 10.1016/s0140-6736(02)08706-8

Open this paper in CoChat — free account

Abstract

There is no one cause of bone fragility; genetic and environmental factors play a part in development of smaller bones, fewer or thinner trabeculae, and thin cortices, all of which result in low peak bone density. Material and structural strength is maintained in early adulthood by remodelling; the focal replacement of old with new bone. However, as age advances less new bone is formed than resorbed in each site remodelled, producing bone loss and structural damage. In women, menopause-related oestrogen deficiency increases remodelling, and at each remodelled site more bone is resorbed and less is formed, accelerating bone loss and causing trabecular thinning and disconnection, cortical thinning and porosity. There is no equivalent midlife event in men, though reduced bone formation and subsequent trabecular and cortical thinning do result in bone loss. Hypogonadism contributes to bone loss in 20-30% of elderly men, and in both sexes hyperparathyroidism secondary to calcium malabsorption increases remodelling, worsening the cortical thinning and porosity and predisposing to hip fractures. Concurrent bone formation on the outer (periosteal) cortical bone surface during ageing partly compensates for bone loss and is greater in men than in women, so internal bone loss is better offset in men. More women than men sustain fractures because their smaller skeleton incurs greater architectural damage and adapts less effectively by periosteal bone formation. The structural basis of bone fragility is determined before birth, takes root during growth, and gains full expression during ageing in both sexes.

Integrity signals

Registry

Crossref · 10.1016/s0140-6736(02)08706-8

Cites

100 of 100 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Prior to puberty there is no sex difference in skeletal features, including height.
“Prior to puberty there is no sex difference in skeletal features, including height (159, 160).”
From Circulating Testosterone as the Hormonal Basis of Sex Differences in Athletic Performance (2018) · cites this paper as [159]

Osteoprotegerin: a novel secreted protein involved in the regulation of bone density.
Simonet, W. S., Lacey, D. L., Dunstan, C. R., Kelley, M., Chang, M.-S., Lüthy, R., Nguyen, H. Q., Wooden, S., Bennett, L., Boone, T., et al. (1997) · Cell · doi:10.1016/s0092-8674(00)80209-3 · Cited by 5,130 · see citing works
Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL
Yasuda, H., Shima, N., Nakagawa, N., Yamaguchi, K., Kinosaki, M., Mochizuki, S.-I., Tomoyasu, A., Yano, K., Goto, M., Murakami, A., et al. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.7.3597 · Cited by 4,224 · see citing works
OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph node organogenesis.
Kong, Y.-Y., Yoshida, H., Sarosi, I., Tan, H.-L., Timms, E., Capparelli, C., Morony, S., Oliveira-dos-Santos, A. J., Van, G., Itie, A., et al. (1999) · Nature · doi:10.1038/16852 · Cited by 3,351 · see citing works
Birth and Death of Bone Cells: Basic Regulatory Mechanisms and Implications for the Pathogenesis and Treatment of Osteoporosis
Manolagas, S. C. (2000) · Endocrine Reviews · doi:10.1210/edrv.21.2.0395 · Cited by 2,575 · see citing works
Osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification.
Bucay, N., Sarosi, I., Dunstan, C. R., Morony, S., Tarpley, J., Capparelli, C., Scully, S., Tan, H. L., Xu, W., Lacey, D. L., et al. (1998) · Genes & Development · doi:10.1101/gad.12.9.1260 · Cited by 2,483 · see citing works
Estrogen Resistance Caused by a Mutation in the Estrogen-Receptor Gene in a Man
Smith, E. P., Boyd, J., Frank, G. R., Takahashi, H., Cohen, R. M., Specker, B., Williams, T. C., Lubahn, D. B., & Korach, K. S. (1994) · New England Journal of Medicine · doi:10.1056/nejm199410203311604 · Cited by 2,471 · see citing works
Modulation of Osteoclast Differentiation and Function by the New Members of the Tumor Necrosis Factor Receptor and Ligand Families
Suda, T., Takahashi, N., Udagawa, N., Jimi, E., Gillespie, M. T., & Martin, T. J. (1999) · Endocrine Reviews · doi:10.1210/edrv.20.3.0367 · Cited by 2,317 · see citing works
LDL Receptor-Related Protein 5 (LRP5) Affects Bone Accrual and Eye Development
Gong, Y., Slee, R. B., Fukai, N., Rawadi, G., Roman-Roman, S., Reginato, A. M., Wang, H., Cundy, T., Glorieux, F. H., Lev, D., et al. (2001) · Cell · doi:10.1016/s0092-8674(01)00571-2 · Cited by 2,235 · see citing works
Differential changes in bone mineral density of the appendicular and axial skeleton with aging: relationship to spinal osteoporosis.
Riggs, B. L., Wahner, H. W., Dunn, W. L., Mazess, R. B., Offord, K. P., & Melton, L. J. (1981) · Journal of Clinical Investigation · doi:10.1172/jci110039 · Cited by 1,194 · see citing works
Effect of testosterone and estradiol in a man with aromatase deficiency
Carani, C., Qin, K., Simoni, M., Faustini-Fustini, M., Serpente, S., Boyd, J., Korach, K. S., & Simpson, E. R. (1997) · New England Journal of Medicine · doi:10.1056/nejm199707103370204 · Cited by 1,151 · see citing works
A Unitary Model for Involutional Osteoporosis: Estrogen Deficiency Causes Both Type I and Type II Osteoporosis in Postmenopausal Women and Contributes to Bone Loss in Aging Men
Riggs, B. L., Khosla, S., & Melton, L. J. (1998) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.1998.13.5.763 · Cited by 1,143 · see citing works
RANK is the intrinsic hematopoietic cell surface receptor that controls osteoclastogenesis, and regulation of bone mass and calcium metabolism.
Li, J., Sarosi, I., Yan, X.-Q., Morony, S., Capparelli, C., Tan, H.-L., McCabe, S., Elliott, R., Scully, S., Van, G., et al. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.4.1566 · Cited by 1,119 · see citing works
Modulation of Osteoclast Differentiation
Suda, T., Takahashi, N., & Martin, T. J. (1992) · Endocrine Reviews · doi:10.1210/edrv-13-1-66 · Cited by 996 · see citing works
Estrogen promotes apoptosis of murine osteoclasts mediated by TGF–β
Hughes, D. E., Dai, A., Tiffee, J. C., Li, H. H., Mundy, G. R., & Boyce, B. F. (1996) · Nature Medicine · doi:10.1038/nm1096-1132 · Cited by 813 · see citing works
Timing of peak bone mass in Caucasian females and its implication for the prevention of osteoporosis. Inference from a cross-sectional model
Matkovic, V, Jelic, T., Wardlaw, G. M., Ilich, J. Z., Goel, P. K., Wright, J. K., Andon, M. B., Smith, K. T., & Heaney, R. P. (1994) · Journal of Clinical Investigation · doi:10.1172/jci117034 · Cited by 806 · see citing works
Relative contributions of testosterone and estrogen in regulating bone resorption and formation in normal elderly men
Falahati-Nini, A., Riggs, B. L., Atkinson, E. J., O’Fallon, W. M., Eastell, R., & Khosla, S. (2000) · Journal of Clinical Investigation · doi:10.1172/jci10942 · Cited by 757 · see citing works
Suppressed Bone Turnover by Bisphosphonates Increases Microdamage Accumulation and Reduces Some Biomechanical Properties in Dog Rib
Mashiba, T., Hirano, T., Turner, C. H., Forwood, M. R., Johnston, C. C., & Burr, D. B. (2000) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.2000.15.4.613 · Cited by 687 · see citing works
SERUM BONE GLA-PROTEIN: A SPECIFIC MARKER FOR BONE FORMATION IN POSTMENOPAUSAL OSTEOPOROSIS
Brown, J. P., Malaval, L., Chapuy, M. C., Delmas, P. D., Edouard, C. M., & Meunier, P. J. (1984) · The Lancet · doi:10.1016/s0140-6736(84)92506-6 · Cited by 667 · see citing works
Osteoclast differentiation factor is a ligand for osteoprotegerin/ osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL. Proc Natl Acad Sci USA 95: 3597-602
Yasuda, H., Shima, N., Nakagawa, N., Yamaguchi, K., Kinosaki, M., Mochizuki, S.-I., Tomoyasu, A., Yano, K., Goto, M., Murakami, A., et al. (1998) · Cited by 650 · see citing works
Reduced Bone Mass in Daughters of Women with Osteoporosis
Seeman, E., Hopper, J. L., Bach, L. A., Cooper, M. E., Parkinson, E., McKay, J., & Jerums, G. (1989) · New England Journal of Medicine · doi:10.1056/nejm198903023200903 · Cited by 631 · see citing works
Self-citation
Increased Bone Mass as a Result of Estrogen Therapy in a Man with Aromatase Deficiency
Bilezikian, J. P., Morishima, A., Bell, J., & Grumbach, M. M. (1998) · New England Journal of Medicine · doi:10.1056/nejm199808273390905 · Cited by 624 · see citing works
Genetic Factors in Determining Bone Mass
Smith, D. M., Nance, W. E., Kang, K.-W., Christian, J. C., & Johnston, C. C. (1973) · Journal of Clinical Investigation · doi:10.1172/jci107476 · Cited by 579 · see citing works
Evidence for two distinct syndromes of involutional osteoporosis
Riggs, B. L., & Melton, L. J. (1983) · The American Journal of Medicine · doi:10.1016/0002-9343(83)90860-4 · Cited by 541 · see citing works
Relationship of Serum Sex Steroid Levels to Longitudinal Changes in Bone Density in Young Versus Elderly Men
Khosla, S. (2001) · Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.86.8.3555 · Cited by 522 · see citing works
DOES BREAST MILK PROTECT AGAINST SEPTICÆMIA IN THE NEWBORN ?
Winberg, J., & Wessner, G. (1971) · The Lancet · doi:10.1016/s0140-6736(71)91836-8 · Cited by 512 · see citing works
Rates of bone loss in the appendicular and axial skeletons of women. Evidence of substantial vertebral bone loss before menopause.
Riggs, B. L., Wahner, H. W., Melton, L. J., Richelson, L. S., Judd, H. L., & Offord, K. P. (1986) · Journal of Clinical Investigation · doi:10.1172/jci112462 · Cited by 511 · see citing works
Cathepsin K Knockout Mice Develop Osteopetrosis Due to a Deficit in Matrix Degradation but Not Demineralization
Gowen, M., Lazner, F., Dodds, R. A., Kapadia, R. D., Feild, J. A., Tavaria, M. D., Bertoncello, I., Drake, F. H., Zavarselk, S., Tellis, I., et al. (1999) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.1999.14.10.1654 · Cited by 491 · see citing works
Disruption of the fibroblast growth factor-2 gene results in decreased bone mass and bone formation
Montero, A., Okada, Y., Tomita, M., Ito, M., Tsurukami, H., Nakamura, T., Doetschman, T., Coffin, J. D., & Hurley, M. M. (2000) · Journal of Clinical Investigation · doi:10.1172/jci8641 · Cited by 483 · see citing works
The mechanical consequences of variation in the mineral content of bone
Currey, J. D. (1969) · Journal of Biomechanics · doi:10.1016/0021-9290(69)90036-0 · Cited by 454 · see citing works
Osteopenia in Men with a History of Delayed Puberty
Finkelstein, J. S., Neer, R. M., Biller, B. M. K., Crawford, J. D., & Klibanski, A. (1992) · New England Journal of Medicine · doi:10.1056/nejm199202273260904 · Cited by 436 · see citing works
The Microanatomy of Trabecular Bone Loss in Normal Aging Men and Women
Aaron, J. E., Makins, N. B., & Sagreiya, K. (1987) · Clinical Orthopaedics and Related Research · doi:10.1097/00003086-198702000-00038 · Cited by 427 · see citing works
Relation of Alleles of the Collagen Type Iα1 Gene to Bone Density and the Risk of Osteoporotic Fractures in Postmenopausal Women
Uitterlinden, A. G., Burger, H., Huang, Q., Yue, F., McGuigan, F. E., Grant, S. F. A., Albert Hofman, D., van Leeuwen, J. P. T. M., Pols, H. A. P., & Ralston, S. H. (1998) · New England Journal of Medicine · doi:10.1056/nejm199804093381502 · Cited by 419 · see citing works
Mean wall thickness of trabecular bone packets in the human iliac crest: Changes with age
Lips, P. T. A. M., Courpron, P., & Meunier, P. J. (1978) · Calcified Tissue International · doi:10.1007/bf02013227 · Cited by 415 · see citing works
The differing tempo of growth in bone size, mass, and density in girls is region-specific
Bass, S. L., Delmas, P. D., Pearce, G., Hendrich, E., Tabensky, A., & Seeman, E. (1999) · Journal of Clinical Investigation · doi:10.1172/jci7060 · Cited by 412 · see citing works
Self-citation
Indian hedgehog couples chondrogenesis to osteogenesis in endochondral bone development
Chung, U. I., Schipani, E., McMahon, A. P., et al. (2001) · Journal of Clinical Investigation · doi:10.1172/jci11706 · Cited by 404 · see citing works
Activated parathyroid hormone/parathyroid hormone–related protein receptor in osteoblastic cells differentially affects cortical and trabecular bone
Calvi, L. M., Sims, N. A., Hunzelman, J. L., Knight, M. C., Giovannetti, A., Saxton, J. M., Kronenberg, H. M., Baron, R., & Schipani, E. (2001) · Journal of Clinical Investigation · doi:10.1172/jci11296 · Cited by 388 · see citing works
Changes in Vertebral Bone Density in Black Girls and White Girls during Childhood and Puberty
Gilsanz, V., Roe, T. F., Mora, S., Costin, G., & Goodman, W. G. (1991) · New England Journal of Medicine · doi:10.1056/nejm199112053252302 · Cited by 386 · see citing works
Trabecular Bone Microarchitecture, Bone Mineral Density, and Vertebral Fractures in Male Osteoporosis
Legrand, É., Chappard, D., Pascaretti, C., Duquenne, M., Krebs, S., Rohmer, V., Baslé, M. F., & Audran, M. (2000) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.2000.15.1.13 · Cited by 381 · see citing works
Cancellous bone remodeling in type i (postmenopausal) osteoporosis: Quantitative assessment of rates of formation, resorption, and bone loss at tissue and cellular levels
Eriksen, E. F., Hodgson, S. F., Eastell, R., Riggs, B., Cedel, S. L., & O’Fallon, W. M. (1990) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.5650050402 · Cited by 366 · see citing works
Volumetric bone mineral density in normal subjects, aged 5-27 years
Lu, P. W., Cowell, C. T., LLoyd-Jones, S. A., BRIODY, J. N., & Howman-Giles, R. B. (1996) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.81.4.8636372 · Cited by 307 · see citing works
From Density to Structure: Growing Up and Growing Old on the Surfaces of Bone
Seeman, E. (1997) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.1997.12.4.509 · Cited by 302 · see citing works
Self-citation
Structural and cellular changes during bone growth in healthy children
PARFITT, A. M., Travers, R., Rauch, F., & Glorieux, F. H. (2000) · Bone · doi:10.1016/s8756-3282(00)00353-7 · Cited by 286 · see citing works
The bone-remodeling transient: Implications for the interpretation of clinical studies of bone mass change
Heaney, R. P. (1994) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.5650091003 · Cited by 286 · see citing works
Assessment of the strength of proximal femur in vitro: Relationship to femoral bone mineral density and femoral geometry
Cheng, X. G., Lowet, G., Boonen, S., Nicholson, P., Brys, P., Nijs, J., & Dequeker, J. (1997) · Bone · doi:10.1016/s8756-3282(96)00383-3 · Cited by 284 · see citing works
Vitamin D–Receptor Gene Polymorphisms and Bone Density in Prepubertal American Girls of Mexican Descent
Sainz, J., Tornout, J. M. V., Loro, M. L., et al. (1997) · New England Journal of Medicine · doi:10.1056/nejm199707103370202 · Cited by 281 · see citing works
Bone Formation Rate in Older Normal Women: Concurrent Assessment with Bone Histomorphometry, Calcium Kinetics, and Biochemical Markers*
Eastell, R., Delmas, P. D., Hodgson, S. F., Eriksen, E. F., Mann, K. G., & Riggs, B. L. (1988) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-67-4-741 · Cited by 273 · see citing works
Differential Effect of Race on the Axial and Appendicular Skeletons of Children1
Gilsanz, V., Skaggs, D. L., Kovanlıkaya, A., Sayre, J. W., Loro, M. L., KAUFMAN, F. R., & Korenman, S. G. (1998) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.83.5.4765 · Cited by 258 · see citing works
Bioavailable Estradiol May Be an Important Determinant of Osteoporosis in Men: The MINOS Study1
Szulc, P., Munoz, F., Claustrat, B., Garnero, P., Marchand, F., Duboeuf, F., & Delmas, P. D. (2001) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.86.1.7126 · Cited by 254 · see citing works
The Earlier Gain and the Later Loss of Cortical Bone: In Nutritional Perspective.
(1971) · Annals of Internal Medicine · doi:10.7326/0003-4819-74-4-652_1 · Cited by 252 · see citing works
Structural Adaptation to Changing Skeletal Load in the Progression Toward Hip Fragility: The Study of Osteoporotic Fractures
Beck, T., Oreskovic, T. L., Stone, K. L., Ruff, C. B., Ensrud, K. E., Nevitt, M. C., Genant, H. K., & Cummings, S. R. (2001) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.2001.16.6.1108 · Cited by 252 · see citing works
Bone homeostasis in growth hormone receptor–null mice is restored by IGF-I but independent of Stat5
Sims, N. A., Clément-Lacroix, P., Ponte, F. D., Bouali, Y., Binart, N., Moriggl, R., Goffin, V., Coschigano, K. T., Gaillard-Kelly, M., Kopchick, J. J., et al. (2000) · Journal of Clinical Investigation · doi:10.1172/jci10753 · Cited by 249 · see citing works
Osteoporosis: Recent Advances in Pathogenesis and Treatment
Barbieri, E. B. (1984) · Journal of Gerontological Nursing · doi:10.3928/0098-9134-19840801-16 · Cited by 238 · see citing works
Consequences of the remodelling process for vertebral trabecular bone structure: a scanning electron microscopy study (uncoupling of unloaded structures)
Mosekilde, L. (1990) · Bone and Mineral · doi:10.1016/0169-6009(90)90046-i · Cited by 237 · see citing works
Osteoporosis: recent advances in pathogenesis and treatment
Cooper, C. C., & Aihie, A. (1994) · QJM · doi:10.1093/oxfordjournals.qjmed.a068917 · Cited by 233 · see citing works
Influence of Puberty on Muscle Area and Cortical Bone Area of the Forearm in Boys and Girls
Schöenau, E., Neu, C. M., Mokov, E., Wassmer, G., & Manz, F. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.85.3.6451 · Cited by 230 · see citing works
Peak trabecular vertebral density: A comparison of adolescent and adult females
Gilsanz, V., Gibbens, D. T., Carlson, M. E., Boechat, M. I., Cann, C. E., & SCHULZ, E. E. (1988) · Calcified Tissue International · doi:10.1007/bf02555144 · Cited by 230 · see citing works
Sex differences in geometry of the femoral neck with aging: A structural analysis of bone mineral data
Beck, T., Ruff, C. B., Scott, W. W., Plato, C. C., Tobin, J. D., & Quan, C. A. (1992) · Calcified Tissue International · doi:10.1007/bf00297293 · Cited by 218 · see citing works
Reference values for trabecular and cortical vertebral bone density in single and dual-energy quantitative computed tomography.
Kalender, W. A., Felsenberg, D., Louis, G. M. B., Lopez, P., Klotz, E., Osteaux, M., & Fraga, J. (1989) · PubMed · Cited by 206 · see citing works
Genetic Regulation of Cortical and Trabecular Bone Strength and Microstructure in Inbred Strains of Mice
Turner, C. H., Hsieh, Y., Müller, R., et al. (2000) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.2000.15.6.1126 · Cited by 205 · see citing works
Sexual Dimorphism in Vertebral Fragility Is More the Result of Gender Differences in Age-Related Bone Gain Than Bone Loss
Duan, Y., Turner, C. H., Kim, B.-T., & Seeman, E. (2001) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.2001.16.12.2267 · Cited by 204 · see citing works
Self-citation
Differential Effect of Race on the Axial and Appendicular Skeletons of Children
Gilsanz, V. (1998) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.83.5.1420 · Cited by 201 · see citing works
Distribution of Intracortical Porosity in Human Midfemoral Cortex by Age and Gender
Bousson, V., Meunier, A., Bergot, C., Vicaut, É., Rocha, M. A., Morais, M. H., Laval-Jeantet, A. M., & Larédo, J.-D. (2001) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.2001.16.7.1308 · Cited by 200 · see citing works
A comparison of iliac bone histomorphometric data in post-menopausal osteoporotic and normal subjects
Kimmel, D. B., Recker, R. R., Gallagher, J. C., Vaswani, A. N., & Aloia, J. F. (1990) · Bone and Mineral · doi:10.1016/0169-6009(90)90061-j · Cited by 194 · see citing works
Vitamin D receptor gene polymorphisms do not predict bone turnover and bone mass in healthy premenopausal women
Garnero, P., Borel, O., Sornay‐Rendu, E., et al. (1995) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.5650100902 · Cited by 194 · see citing works
A longitudinal evaluation of bone mineral density in adult men with histories of delayed puberty.
Finkelstein, J. S., Klibanski, A., & Neer, R. M. (1996) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.81.3.8772591 · Cited by 179 · see citing works
Growth in Bone Mass and Size—Are Racial and Gender Differences in Bone Mineral Density More Apparent than Real?
Seeman, E., & D., M. (1998) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.83.5.4844 · Cited by 177 · see citing works
Self-citation
Mechanisms by which cells of the osteoblast lineage control osteoclast formation and activity
Martin, T. J., & Ng, K. W. (1994) · Journal of Cellular Biochemistry · doi:10.1002/jcb.240560312 · Cited by 173 · see citing works
Bioavailable Estradiol May Be an Important Determinant of Osteoporosis in Men: The MINOS Study
Szulc, P. (2001) · Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.86.1.192 · Cited by 169 · see citing works
Trabecular architecture in women and men of similar bone mass with and without vertebral fracture: II. three-dimensional histology
Aaron, J. E., Shore, P. A., Shore, R. F., Beneton, M. N. C., & Kanis, J. A. (2000) · Bone · doi:10.1016/s8756-3282(00)00328-8 · Cited by 166 · see citing works
Vertebral Bone Mass, Size, and Volumetric Density in Women with Spinal Fractures
Duan, Y., Parfitt, A. M., & Seeman, E. (1999) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.1999.14.10.1796 · Cited by 162 · see citing works
Self-citation
Femoral neck geometry and radiographic signs of osteoporosis as predictors of hip fracture
Karlsson, K. M., Sernbo, I., Obrant, K. J., Redlund-Johnell, I., & Johnell, O. (1996) · Bone · doi:10.1016/8756-3282(96)00004-x · Cited by 161 · see citing works
Vertebral size in elderly women with osteoporosis. Mechanical implications and relationship to fractures.
Gilsanz, V., Loro, M. L., Roe, T., Sayre, J. W., Gilsanz, R., & Schulz, E. (1995) · Journal of Clinical Investigation · doi:10.1172/jci117925 · Cited by 159 · see citing works
The Effect of Vitamin D Supplementation on the Bone Mineral Density of the Femoral Neck Is Associated with Vitamin D Receptor Genotype
Graafmans, W. C., Lips, P. T. A. M., Ooms, M., van Leeuwen, J. P. T. M., Pols, H. A. P., & Uitterlinden, A. G. (1997) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.1997.12.8.1241 · Cited by 148 · see citing works
Unequal decrease in bone density of lumbar spine and ultradistal radius in Colles' and vertebral fracture syndromes.
Eastell, R., Wahner, H. W., O’Fallon, W. M., et al. (1989) · Journal of Clinical Investigation · doi:10.1172/jci113854 · Cited by 141 · see citing works
Early Identification of Children Predisposed to Low Peak Bone Mass and Osteoporosis Later in Life1
Loro, M. L., Sayre, J. W., Roe, T. F., Goran, M. I., KAUFMAN, F. R., & Gilsanz, V. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.85.10.6887 · Cited by 138 · see citing works
Fracture Site-Specific Deficits in Bone Size and Volumetric Density in Men with Spine or Hip Fractures
Seeman, E., Duan, Y., Fong, C., & Edmonds, J. (2001) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.2001.16.1.120 · Cited by 133 · see citing works
Self-citation
Spatial clustering of remodeling osteons in the femoral neck cortex: a cause of weakness in hip fracture?
Jordan, G. R., Loveridge, N., Bell, K. L., Power, J., Rushton, N., & REEVE, J. (2000) · Bone · doi:10.1016/s8756-3282(99)00272-0 · Cited by 130 · see citing works
Normal Volumetric Bone Mineral Density and Bone Turnover in Young Men with Histories of Constitutional Delay of Puberty
Bertelloni, S., Baroncelli, G. I., Ferdeghini, M., Perri, G., & Saggese, G. (1998) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.83.12.5348 · Cited by 124 · see citing works
Heterogeneity in the Growth of the Axial and Appendicular Skeleton in Boys: Implications for the Pathogenesis of Bone Fragility in Men
Bradney, M., Karlsson, M. K., Duan, Y., STUCKEY, S. L., Bass, S. L., & Seeman, E. (2000) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.2000.15.10.1871 · Cited by 121 · see citing works
Self-citation
Early Identification of Children Predisposed to Low Peak Bone Mass and Osteoporosis Later in Life
Loro, M. L. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.85.10.3908 · Cited by 121 · see citing works
Trabecular architecture in women and men of similar bone mass with and without vertebral fracture: I. two-dimensional histology
Hordon, L. D., Raisi, M., Aaron, J. E., Paxton, S., Beneton, M. N. C., & Kanis, J. А. (2000) · Bone · doi:10.1016/s8756-3282(00)00329-x · Cited by 111 · see citing works
Structural and geometric changes in iliac bone: Relationship to normal aging and osteoporosis
Földes, J., PARFITT, A. M., Shih, M. S., et al. (1991) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.5650060714 · Cited by 110 · see citing works
A TA Repeat Polymorphism in the Estrogen Receptor Gene Is Associated with Osteoporotic Fractures but Polymorphisms in the First Exon and Intron Are Not
Langdahl, B. L., Løkke, E., Carstens, M., Stenkjær, L. L., & Eriksen, E. F. (2000) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.2000.15.11.2222 · Cited by 110 · see citing works
Bone Mass in Middle-Aged Osteoporotic Men and Their Relatives: Familial Effect
Cohen-Solal, M. E., Baudoin, C., Omouri, M., Kuntz, D., & de Vernejoul, M. C. (1998) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.1998.13.12.1909 · Cited by 108 · see citing works
Bone Mineral Density and Bone Size in Men With Primary Osteoporosis and Vertebral Fractures
Vega, E., Ghiringhelli, G., Mautalén, C., et al. (1998) · Calcified Tissue International · doi:10.1007/s002239900462 · Cited by 102 · see citing works
Bone Structure in Patients with Low Bone Mineral Density With or Without Vertebral Fractures
Oleksik, A., Ott, S. M., Vedi, S., et al. (2000) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.2000.15.7.1368 · Cited by 101 · see citing works
Measurement of femoral geometry in type I and type II osteoporosis: Differences in hip axis length consistent with heterogeneity in the pathogenesis of osteoporotic fractures
Boonen, S., Koutri, R., Dequeker, J., et al. (1995) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.5650101210 · Cited by 101 · see citing works
On Exposure to Anorexia Nervosa, the Temporal Variation in Axial and Appendicular Skeletal Development Predisposes to Site-Specific Deficits in Bone Size and Density: A Cross-Sectional Study
Seeman, E., Karlsson, M. K., & Duan, Y. (2000) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.2000.15.11.2259 · Cited by 93 · see citing works
Self-citation
The Effects of Gonadectomy on Bone Size, Mass, and Volumetric Density in Growing Rats Are Gender-, Site-, and Growth Hormone–Specific
Zhang, X. Z., Kalu, D. N., Erbas, B., Hopper, J. L., & Seeman, E. (1999) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.1999.14.5.802 · Cited by 79 · see citing works
Self-citation
Urinary excretion of type I collagen crosslinked N-telopeptides in Healthy japanese adults: Age- and sex-related changes and reference limits
Sone, T., Miyake, M., Takeda, N., et al. (1995) · Bone · doi:10.1016/s8756-3282(95)00243-x · Cited by 70 · see citing works
A STUDY OF BONE GROWTH IN NORMAL CHILDREN AND ITS RELATIONSHIP TO SKELETAL MATURATION
Tupman, G. S. (1962) · Journal of Bone and Joint Surgery - British Volume · doi:10.1302/0301-620x.44b1.42 · Cited by 65 · see citing works
Interaction of the effects between vitamin D receptor polymorphism and exercise training on bone metabolism
Tajima, O., Ashizawa, N., Ishii, T., et al. (2000) · Journal of Applied Physiology · doi:10.1152/jappl.2000.88.4.1271 · Cited by 64 · see citing works
The Contribution of Reduced Peak Accrual of Bone and Age-Related Bone Loss to Osteoporosis at the Spine and Hip: Insights from the Daughters of Women with Vertebral or Hip Fractures
Tabensky, A., Duan, Y., Edmonds, J., & Seeman, E. (2001) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.2001.16.6.1101 · Cited by 62 · see citing works
Self-citation
Evaluation of cortical thickness and bone density by roentgen microdensitometry in growing males and females
Zamberlan, N., Radetti, G., Paganini, C., Gatti, D., Rossini, M., Braga, V., & Adami, S. (1996) · European Journal of Pediatrics · doi:10.1007/bf01955265 · Cited by 61 · see citing works
Genetics of Fracture: Challenges and Opportunities
Nguyen, T. V., & Eisman, J. A. (2000) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.2000.15.7.1253 · Cited by 59 · see citing works
Lack of Influence of Collagen Type Iα1 Sp1 Binding Site Polymorphism on the Rate of Bone Loss in a Cohort of Postmenopausal Danish Women Followed for 18 Years
Heegaard, A., Jørgensen, H. L., Vestergaard, A., et al. (2000) · Calcified Tissue International · doi:10.1007/s002230010083 · Cited by 55 · see citing works
VDR Genotype and Response to Etidronate Therapy in Late Postmenopausal Women
Marc, J., Preželj, J., Komel, R., et al. (1999) · Osteoporosis International · doi:10.1007/s001980050231 · Cited by 51 · see citing works
The Association Between Heel Ultrasound and Hormone Replacement Therapy Is Modulated by a Two-Locus Vitamin D and Estrogen Receptor Genotype
Giguère, Y., Dodin, S., Blanchet, C., et al. (2000) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.2000.15.6.1076 · Cited by 50 · see citing works
Association of Transforming Growth Factor β1 Genotype with Therapeutic Response to Active Vitamin D for Postmenopausal Osteoporosis
Yamada, Y., Harada, A., Hosoi, T., Miyauchi, A., Ikeda, K., Ohta, H., & Shiraki, M. (2000) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.2000.15.3.415 · Cited by 50 · see citing works
Association of a polymorphism of the transforming growth factor beta-1 gene with prevalent vertebral fractures in Japanese women
Yamada, Y., Miyauchi, A., Takagi, Y., Nakauchi, K., 三木, 信., Mizuno, M., & Harada, A. (2000) · The American Journal of Medicine · doi:10.1016/s0002-9343(00)00468-x · Cited by 29 · see citing works

Flagged first, then by citations

Sorted by citations

Estrogens and androgens in skeletal physiology and pathophysiology
Almeida, M., Laurent, M. R., Dubois, V., Claessens, F., O'Brien, C. A., Bouillon, R., Vanderschueren, D., & Manolagas, S. C. (2017) · Physiological Reviews · doi:10.1152/physrev.00033.2015 · Cited by 860 · see citing works
Targeted ablation of osteocytes induces osteoporosis with defective mechanotransduction.
Tatsumi, S., Ishii, K., Amizuka, N., Li, M., Kobayashi, T., Kohno, K., Ito, M., Takeshita, S., & Ikeda, K. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2007.05.001 · Cited by 848 · see citing works
Androgens and Bone
Vanderschueren, D., Vandenput, L., Boonen, S., Lindberg, M. K., Bouillon, R., & Ohlsson, C. (2004) · Endocrine Reviews · doi:10.1210/er.2003-0003 · Cited by 717 · see citing works
Gender Disparities in Osteoporosis
Alswat, K. A. (2017) · Journal of Clinical Medicine Research · doi:10.14740/jocmr2970w · Cited by 596 · see citing works
Circulating Testosterone as the Hormonal Basis of Sex Differences in Athletic Performance
Handelsman, D. J., Hirschberg, A. L., & Bermon, S. (2018) · Endocrine Reviews · doi:10.1210/er.2018-00020 · Cited by 594 · see citing works
Epidemiology of fracture risk with advancing age
Ensrud, K. E. (2013) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/glt092 · Cited by 456 · see citing works
Chronic kidney disease and bone fracture: A growing concern
Nickolas, T. L., Leonard, M. B., & Shane, E. (2008) · Kidney International · doi:10.1038/ki.2008.264 · Cited by 300 · see citing works
Osteoblasts in osteoporosis: Past, emerging, and future anabolic targets
Marie, P. J., & Kassem, M. (2011) · European Journal of Endocrinology · doi:10.1530/eje-11-0132 · Cited by 234 · see citing works
PTH receptor signaling in osteocytes governs periosteal bone formation and intracortical remodeling
Rhee, Y., Allen, M. R., Condon, K., Lezcano, V., Ronda, A. C., Galli, C., Olivos, N., Passeri, G., O'Brien, C. A., Bivi, N., et al. (2011) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.304 · Cited by 208 · see citing works
BMI and BMD: the potential interplay between obesity and bone fragility
Palermo, A., Tuccinardi, D., Defeudis, G., Watanabe, M., D’Onofrio, L., Lauria Pantano, A., Napoli, N., Pozzilli, P., & Manfrini, S. (2016) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph13060544 · Cited by 197 · see citing works
Bone geometry and skeletal fragility
Bouxsein, M. L., & Karasik, D. (2006) · Current Osteoporosis Reports · doi:10.1007/s11914-006-0002-9 · Cited by 165 · see citing works
The pathophysiology of osteoporosis in obesity and type 2 diabetes in aging women and men: The mechanisms and roles of increased bone marrow adiposity
Ali, D., Tencerova, M., Figeac, F., Kassem, M., & Jafari, A. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.981487 · Cited by 122 · see citing works
“Aging is associated with significant bone loss and structural bone damage, due to accelerated trabecular thinning and disconnection, cortical thinning, and porosity (12), leading to increased fracture risk.”
Background
TGFβ-induced degradation of TRAF3 in mesenchymal progenitor cells causes age-related osteoporosis
Li, J., Ayoub, A., Xiu, Y., Yin, X., Sanders, J. O., Mesfin, A., Xing, L., Yao, Z., & Boyce, B. F. (2019) · Nature Communications · doi:10.1038/s41467-019-10677-0 · Cited by 86 · see citing works
Adaptation of the Skeletal System During Long-Duration Spaceflight
Sibonga, J. D., Cavanagh, P. R., Lang, T. F., LeBlanc, A. D., Schneider, V. S., Shackelford, L. C., Smith, S. M., & Vico, L. (2007) · Clinical Reviews in Bone and Mineral Metabolism · doi:10.1007/s12018-008-9012-8 · Cited by 67 · see citing works
Impact of Aromatase Inhibitor Therapy on Bone Turnover, Cortical Bone Growth and Vertebral Morphology in Pre- and Peripubertal Boys with Idiopathic Short Stature
Hero, M., Mäkitie, O., Kröger, H., Nousiainen, E., Toiviainen-Salo, S., & Dunkel, L. (2009) · Hormone Research in Paediatrics · doi:10.1159/000208803 · Cited by 60 · see citing works
ORIGINAL ARTICLE: The association between serum thyrotropin (TSH) levels and bone mineral density in healthy euthyroid men
Kim, B., Lee, S. H., Bae, S. J., Kim, H. K., Choe, J. W., Kim, H. Y., Koh, J., & Kim, G. S. (2010) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2010.03818.x · Cited by 43 · see citing works
Diet and exercise during growth have site-specific skeletal effects: a co-twin control study
Iuliano-Burns, S., Stone, J., Hopper, J. L., & Seeman, E. (2005) · Osteoporosis International · doi:10.1007/s00198-004-1830-z · Cited by 34 · see citing works
Self-citation

Effects of N,N,N?,N?-ethylenediaminetetramethylene phosphonic acid on cortical bone remodeling in the adult dog
JEE, W. (1988) · Toxicology and Applied Pharmacology · doi:10.1016/0041-008x(88)90173-1 · Cited by 4 · see citing works
Bone Turnover in Bone Biopsies of Patients with Low-Energy Cortical Fractures Receiving Bisphosphonates: A Case Series
Armamento‐Villareal, R., Napoli, N., Diemer, K., Watkins, M. P., Civitelli, R., Teitelbaum, S. L., & Novack, D. V. (2009) · Calcified Tissue International · doi:10.1007/s00223-009-9263-5 · Cited by 118 · see citing works
Genetics of osteoporosis: How/what to do?
Deng, H. (2010) · Bone · doi:10.1016/j.bone.2010.09.057
Early Changes in Biochemical Markers of Bone Turnover Are Associated with Long-Term Changes in Bone Mineral Density in Elderly Women on Alendronate, Hormone Replacement Therapy, or Combination Therapy: A Three-Year, Double-Blind, Placebo-Controlled, Randomized Clinical Trial
Greenspan, S. L., Resnick, N. M., & Parker, R. A. (2005) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2004-1091 · Cited by 103 · see citing works
Separate assessment of forearm cortical and trabecular bone density from standard densitometry data
Boyanov, M., Popivanov, P. R., & Roux, C. H. (2001) · Annals of Medicine · doi:10.3109/07853890109002100 · Cited by 8 · see citing works

Authors: Seeman, E.
Affiliations: Heidelberg Repatriation Hospital (AU)
Corresponding author: Seeman, Ego
ORCID: Seeman, Ego
Venue: The Lancet
Publisher: Elsevier BV
Published: 2002-05
Volume: 359
Issue: 9320
Pages: 1841-1850
ISSN: 0099-5355 (ISSN-L)
0140-6736
DOI: 10.1016/s0140-6736(02)08706-8
OpenAlex: W2056810908
Cited by: 909
References: 100
Citations by year: 2026: 12 · 2025: 26 · 2024: 29 · 2023: 28 · 2022: 28 · 2021: 23 · 2020: 40 · 2019: 34 · 2018: 40 · 2017: 35 · 2016: 30 · 2015: 38 · 2014: 39 · 2013: 42 · 2012: 47
FWCI: 7.50
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: The Lancet (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
Health Sciences › Medicine › Epidemiology › Bone fractures and treatments
Keywords: bone fragility, osteoporosis, bone loss, bone remodeling, peak bone mass, cortical thinning, bone porosity, menopause, estrogen deficiency, hypogonadism, hyperparathyroidism, calcium malabsorption, hip fracture, sex differences, aging, periosteal bone formation, bone structure
MeSH terms: Adolescent, Aged, Aging, Bone Development, Female, Humans, Male, Osteoporosis, Sex Factors, Bone Density, Bone Remodeling

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Pathogenesis of bone fragility in women and men

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Cites

Cited by

Related

Record

About these checks